New biomarker identified for hepatocellular carcinoma

Serum WFA+-M2BP is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis C patients who achieved sustained virological responses (SVR) after treatment with interferon-free, direct acting antivirals (DAAs), according to a new study in Hepatology Research.

The advent of DAAs has dramatically improved the success of antiviral therapy. Experts suspect a decreased risk of HCC with SVR; nevertheless, it remains to be seen whether DAAs reduce the risk of HCC development.

“Wisteria floribunda agglutinin positive Mac-2 binding protein (WFA+-M2BP) is a novel serum biomarker which shows significant correlation with liver fibrosis in patients with chronic hepatitis B, C, non-alcoholic fatty liver disease, and primary biliary cholangitis,” wrote authors, led by Yutaka Yasui, MD, PhD, Department of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo. “This serum marker also has been reported as a predictive marker for the development of HCC.”

To date, most studies have assessed the predictive value of WFA+-M2BP with regard to liver fibrosis, development of HCC, and overall survival in patients with ongoing HCV infection. In the current study, the authors aimed to elucidate the predictive value of this biomarker in patients with chronic hepatitis C who attained SVR after treatment with interferon-free DAAs.

In this retrospective cohort study, the researchers assessed 567 patients (40.6% men; mean age=66 years) who attained SVR after 12 weeks of treatment with interferon-free DAAs. The team collected data at baseline, or before treatment commenced, and after SVR was achieved at 12 weeks.

Laboratory tests included transaminases, albumin, bilirubin, cholesterol, platelet counts, alpha-fetoprotein (AFP), and serum WFA+-M2BP. Histology was also available for some patients who underwent liver biopsy before the initiation of DAA therapy.

The primary outcome was the development of HCC in patients with no history of the disease or the recurrence of HCC in patients who had been previously received curative treatment. The researchers analyzed the data for factors predictive of either the occurrence or recurrence of HCC, after stratifying for previous HCC treatment.

In total, 13 of 518 patients with no previous history of HCC went on to develop HCC, after a median follow-up period of 351 days. The team found that post-SVR WFA+-M2BP ≥ 1.75 cut off index (P < 0.001) and alpha-fetoprotein (AFP) level ≥ 6 ng/ml (P=0.01) served as significant predictors of HCC occurrence. On multivariate analysis, post-SVR WFA+-M2BP ≥ 1.75 COI was found to be a significant predictor of HCC occurrence with a hazard ratio (HR) of 6.0 (95% CI = 1.8-19.4; P = 0.003).

In total, 22 of 49 patients with a previous history of HCC went on to experience recurrence after SVR, with a median time of 535 days. Post-SVR AFP ≥ 6 ng/ml was the only factor correlated with recurrence-free survival.

Per results of pre-treatment biopsy, the team found that 170 of 470 patients showed evidence of advanced fibrosis, and 50 patients had evidence of cirrhosis.

“First, we showed that this serum marker is useful for predicting the de novo development of HCC in patients who have achieved SVR with interferon-free therapy,” the authors wrote. “Second, in patients who had a history of HCC, a higher cut-off of WFA+-M2BP showed a tendency to correlate with recurrence, along with post-SVR AFP.”

The authors suggested that the reason that WFA+-M2BP could predict HCC development is that this biomarker indicates the degree of liver fibrosis post-SVR better than either a baseline liver biopsy or baseline WFA+-M2BP value.

Of interest, the investigators observed a positive association between post-SVR WFA+-M2BP and alanine transaminase levels.

“This might suggest that post-SVR WFA+-M2BP levels indicate to some extent the potential of residual liver inflammation, which could be a risk factor for future HCC development,” wrote the authors.

The authors noted limitations in the current study. For example, this retrospective study was prone to selection bias. In addition, the follow-up period in the current study was short, with longer prospective studies needed.

“WFA+-M2BP is a predictive factor for the development of HCC in DAA-treated patients with no history of HCC,” the authors concluded. “In contrast, the post-SVR AFP level is a predictive factor for HCC recurrence.”

This study was funded by the Japan Agency for Medical Research and Development.